Association of Cyclooxygenase-1-Dependent and -Independent Platelet Function Assays With Adverse Clinical Outcomes in Aspirin-Treated Patients Presenting for Cardiac Catheterization

被引:137
作者
Frelinger, Andrew L., III [1 ,2 ,3 ]
Li, YouFu [2 ,3 ]
Linden, Matthew D. [2 ,3 ]
Barnard, Marc R. [1 ,2 ,3 ]
Fox, Marsha L. [2 ,3 ]
Christie, Douglas J. [4 ]
Furman, Mark I. [5 ]
Michelson, Alan D. [1 ,2 ,3 ]
机构
[1] Harvard Univ, Div Hematol Oncol, Ctr Platelet Res Studies, Childrens Hosp Boston,Sch Med, Boston, MA 02115 USA
[2] Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Dept Pediat, Worcester, MA USA
[3] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA
[4] Siemens Healthcare Diagnost, Newark, DE USA
[5] S Shore Hosp, S Weymouth, MA USA
关键词
aspirin; myocardial infarction; platelets; revascularization; thromboxane; ACUTE CORONARY SYNDROMES; CARDIOVASCULAR EVENTS; THROMBOXANE BIOSYNTHESIS; ADENOSINE-DIPHOSPHATE; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; HIGH-RISK; RESISTANCE; CLOPIDOGREL; DISEASE;
D O I
10.1161/CIRCULATIONAHA.109.900589
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Poor clinical outcome in aspirin-treated patients has been termed aspirin resistance and may result from inadequate inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin. The objectives of this study were to determine prospectively whether COX-1-dependent and other platelet function assays correlate with clinical outcomes in aspirin-treated patients. Methods and Results-Blood was collected before percutaneous coronary intervention from 700 consecutive aspirin-treated (81 or 325 mg for >= 3 days) patients. Platelet function was tested by (1) serum thromboxane B(2); (2) arachidonic acid-stimulated platelet surface P-selectin and activated glycoprotein IIb/IIIa and leukocyte-platelet aggregates; and (3) platelet function analyzer (PFA)-100 collagen-epinephrine and collagen-ADP closure time (CT). Adverse clinical outcomes of all-cause death, cardiovascular death, and major adverse cardiovascular events (cardiovascular death, myocardial infarction, hospitalization for revascularization, or acute coronary syndrome) were assessed by telephone interview and/or medical record review. Clinical outcomes information was obtained at 24.8 +/- 0.3 months after platelet function testing. By univariate analysis, COX-1-dependent assays, including serum thromboxane B(2) level, were not associated with adverse clinical outcomes, whereas the COX-1-independent assay, PFA-100 collagen-ADP CT < 65 seconds, was associated with major adverse cardiovascular events (P = 0.0149). After adjustment for covariables (including sex, aspirin dose, Thrombolysis in Myocardial Infarction risk score, clopidogrel use), both serum thromboxane B(2) > 3.1 ng/mL and PFA-100 collagen-ADP CT < 65 seconds were associated with major adverse cardiovascular events. In contrast, indirect measures of platelet COX-1 (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT) were not significantly associated with adverse clinical outcomes even after adjustment for covariables. Conclusions-In this prospective study of 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease, residual platelet COX-1 function measured by serum thromboxane B(2) and COX-1-independent platelet function measured by PFA-100 collagen-ADP CT, but not indirect COX-1-dependent assays (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT), correlate with subsequent major adverse cardiovascular events. This study suggests that multiple mechanisms, including but not confined to inadequate inhibition of COX-1, are responsible for poor clinical outcomes in aspirin-treated patients, and therefore the term aspirin resistance is inappropriate. (Circulation. 2009;120:2586-2596.)
引用
收藏
页码:2586 / 2596
页数:11
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